Second-Line Treatment for Patients With Platinum-Sensitiv... | NCT00090610

ID	Type	Description	Link
DUKE UNIVERSITY MEDICAL CENTER	Other Identifier	Duke UMC
DUMC03

Name	Class
Aventis Pharmaceuticals	INDUSTRY

Description Module

Detailed Description

Primary Objective

The primary objective of the study is to compare the progression-free survival of two treatment regimens:

Taxotere® 30 mg/m2 IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days for 6 cycles or until disease progression. (A patient who has completed 6 cycles of treatment and who has achieved a partial response or stable disease may either continue or stop treatment at the investigator's discretion.)

Versus

Taxotere® 30 mg/m2 IV on Days 1 and 8, repeated every 21 days up to 6 cycles or until disease progression. Followed by carboplatin (AUC 6) IV every 21 days if the patient does not achieve a complete response or has disease progression on Taxotere®. A patient who has achieved a complete response on Taxotere® will be followed until the subsequent recurrence at which time she will then receive single-agent carboplatin. Carboplatin treatment will be discontinued if the patient has completed 6 cycles of treatment and has achieved a complete response or has disease progression. (A patient who has completed 6 cycles of carboplatin treatment and who has achieved a partial response or stable disease may either continue or stop treatment at the investigator's discretion.)

Secondary Objectives

The secondary objectives of the study are to compare the objective response rates (defined as a complete response plus partial response), duration of tumor response, median survival, QOL and safety in patients treated with the two regimens described above.

Label	Type	Description	Intervention Names
Arm 1 - Combination Therapy	Experimental	Docetaxel 30mg/m2 mg IV on Days 1 and 8, in combination with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression	Drug: Docetaxel Drug: Carboplatin
Arm 2 - Sequential Therapy	Experimental	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression. Once subjects have completed 6 cycles of docetaxel, they receive carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.	Drug: Docetaxel Drug: Carboplatin

Name	Type	Description	Arm Group Labels	Other Names
Docetaxel	Drug	For Arm 1: 30mg/m2 mg IV on Days 1 and 8 repeated every 21 days for six cycles until disease progression combined with carboplatin For Arm 2: 30mg/m2 IV on Days 1 and 8 repeated every 21 days for six cycles until disease progression followed by carboplatin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS)	Progression in measurable disease is defined as any of the following: At least a 20% increase in the sum of the longest diameter target lesions; appearance of one or more new lesions; Death due to disease without prior objective documentation of progression; deterioration in health status attributable to the disease requiring a change in therapy without objective documentation of progression Progression in non-measurable disease according to CA125 levels is defined as any of the following: CA125 that begins in normal range increases to twice the upper limit of normal; CA125 level that begins elevated increases 25% over two previous samples, a 50% increase over three previous samples, or a persistent elevation over 100 U/ml for more than 2 months without a 50% decrease.	Every 6 months, to 18 months

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate	Complete response rate plus partial response rate, where: Complete response (CR) is defined as disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart and normalization of elevated CA125 in cases of ovarian cancer; Partial response (PR) for measurable disease is defined >= 30% decrease in the sum of the longest dimensions of all target measurable lesions with no unequivocal progression of non-target lesions as well as no new lesions, with documentation by two disease assessments at least four weeks apart. PR according to CA125 levels is defined as a 50% decrease in CA125 levels where two initial samples were elevated and the sample that shows the 50% is confirmed by a fourth sample 28 days after the prior sample. OR = CR + PR

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Pathologically confirmed epithelial ovarian cancer, peritoneal serous cancer, or tubal carcinoma.
The patient's tumor is platinum-sensitive, which means that the patient had a complete response to front-line treatment with a platinum compound and had a treatment-free interval without clinical evidence of progressive disease for greater than 6 months.
The patient has received one and only one prior chemotherapy regimen for the treatment of this malignancy. Prior treatment with paclitaxel and/or a platinum compound is allowed. Patients who have received consolidation treatment are allowed. Prior treatment with Taxotere® is not allowed.

o Consolidation therapy is allowed including a different cytotoxic agent than the agent used in the front-line regimen, intraperitoneal therapy, biologic therapy, and immunotherapy.
Patients may have received one prior regimen with a biologic therapy, either combined with cytotoxic therapy in the front-line setting, or as a single-agent for this recurrence. The biologic therapy must be discontinued at least three weeks prior to registration.
Measurable or evaluable disease either by radiologic imaging, or physical exam, or by measurement of CA125 < 70 on two occasions at least one week apart.
At least 3 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal.
At least 3 weeks since major surgery, with full recovery. Patients who have undergone a secondary tumor debulking or cytoreductive surgery for this malignancy are excluded.
Eastern Cooperative Oncology Group (ECOG) performance status < 2.
Age > 18 years.
Absolute neutrophil count > 1,500/mm3; platelet count > 100,000/mm3; Hemoglobin > 8.0 g/dl
Serum bilirubin Within Normal Limits (WNL); AST or ALT and Alkaline Phosphatase must be within the range allowing for eligibility.
If there is childbearing potential, a serum pregnancy test must be negative.
Patients of childbearing potential must be willing to consent to using effective contraception while on treatment and for three months following the completion of treatment.
Informed consent has been obtained.

Exclusion Criteria:

Prior treatment with Taxotere®.
Concurrent immunotherapy or hormonal therapy for the specific purpose of treatment for the disease. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to enrollment in order for the patient to be eligible to participate in this trial. Continuation of Hormone Replacement therapy is permitted.
Serious concurrent medical or psychiatric illness, including serious active infection.
Peripheral neuropathy > grade 2.
History of other malignancy within the last 5 years, except for basal cell skin carcinoma.
The patient is pregnant or nursing.
Patients with a history of severe hypersensitivity reaction to cisplatin, carboplatin, mannitol, or drugs formulated with Polysorbate 80.
Secondary debulking for this recurrence.

Name	Affiliation	Role
Angeles A Secord, MD	Duke University	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Florida Gynecologic Oncology		Fort Myers	Florida	33901	United States
Jupiter Medical Center-Gynecology Oncology and Gynecology

PubMed Identifier	Type	Citation	Retractions
22072307	Result	Alvarez Secord A, Berchuck A, Higgins RV, Nycum LR, Kohler MF, Puls LE, Holloway RW, Lewandowski GS, Valea FA, Havrilesky LJ. A multicenter, randomized, phase 2 clinical trial to evaluate the efficacy and safety of combination docetaxel and carboplatin and sequential therapy with docetaxel then carboplatin in patients with recurrent platinum-sensitive ovarian cancer. Cancer. 2012 Jul 1;118(13):3283-93. doi: 10.1002/cncr.26610. Epub 2011 Nov 9.
21945310

ID	Title	Description
FG000	Arm 1	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression
FG001	Arm 2	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.

ID	Title	Description
BG000	Arm 1	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression
BG001	Arm 2	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-free Survival (PFS)

Progression in measurable disease is defined as any of the following: At least a 20% increase in the sum of the longest diameter target lesions; appearance of one or more new lesions; Death due to disease without prior objective documentation of progression; deterioration in health status attributable to the disease requiring a change in therapy without objective documentation of progression

Progression in non-measurable disease according to CA125 levels is defined as any of the following: CA125 that begins in normal range increases to twice the upper limit of normal; CA125 level that begins elevated increases 25% over two previous samples, a 50% increase over three previous samples, or a persistent elevation over 100 U/ml for more than 2 months without a 50% decrease.

1 patient in each arm was excluded. The patient in Arm 1 did not complete 1 cycle of therapy. A patient in Arm 2 withdrew from the study

Posted

Median

95% Confidence Interval

months

Every 6 months, to 18 months

ID	Title	Description
OG000	Arm 1	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression
OG001	Arm 2	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.

Units	Counts
Participants	OG00074 OG00174

Title

Denominators

Categories

Title	Measurements
	OG00013.7(9.9 to 16.8) OG0018.4(7.1 to 11.0)

Secondary

Objective Response Rate

Complete response rate plus partial response rate, where: Complete response (CR) is defined as disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart and normalization of elevated CA125 in cases of ovarian cancer; Partial response (PR) for measurable disease is defined >= 30% decrease in the sum of the longest dimensions of all target measurable lesions with no unequivocal progression of non-target lesions as well as no new lesions, with documentation by two disease assessments at least four weeks apart. PR according to CA125 levels is defined as a 50% decrease in CA125 levels where two initial samples were elevated and the sample that shows the 50% is confirmed by a fourth sample 28 days after the prior sample.

OR = CR + PR

Same as for PFS

Posted

Number

95% Confidence Interval

percentage of participants

Every 6 months, starting at 12 months to 24 months

ID	Title	Description
OG000	Arm 1	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression
OG001	Arm 2	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.

Secondary

Quality of Life

Quality of Life was measured using the Trial Outcome Index (TOI) score of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) instrument, version 4. The TOI portion of the FACT-O included questions related to Physical well-being (PWB), Social/Family well-being (FWB), and an ovarian cancer specific module (OCS). The PWB score range is from 0-28; the FWB score range is from 0-28; the OCS score range is from 0-44; this gives the TOI a score range from 0-100. (TOI = PWB + FWB + OCS)

With these instruments, a higher score indicates better health-related quality of life.

The number of participants was based on QoL data available for Arm 1 and one patient withdrew on Arm 2.

Posted

Mean

Standard Deviation

units on a scale

Baseline performed 14 days before first dose, then every other cycle and at study termination

ID	Title	Description
OG000	Arm 1	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression
OG001	Arm 2	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.

Secondary

Recurrence-Free Survival

Recurrence-free survival is based on measurable disease using Kaplan-Meier estimates for the intent to treat (ITT) Population who achieved a complete response.

Subjects who had a complete response.

Posted

Median

95% Confidence Interval

months

Every 6 months starting at 12 months, to 24 months

ID	Title	Description
OG000	Arm 1	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression
OG001	Arm 2	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.

Units	Counts
Participants	OG000

Secondary

Median Overall Survival

Posted

Median

95% Confidence Interval

months

Every 6 months starting at 12 months, to 24 months

ID	Title	Description
OG000	Arm 1	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression
OG001	Arm 2	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Intestinal obstruction	Gastrointestinal disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0017 events7 affected74 at risk
allergic reaction	Immune system disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0011 events1 affected74 at risk
diarrhea	Gastrointestinal disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected74 at risk
tongue edema	Gastrointestinal disorders	CTCAE 3.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected74 at risk
vomiting	Gastrointestinal disorders	CTCAE 3.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected74 at risk
Infection	Infections and infestations	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0013 events3 affected74 at risk
Deep Thrombophlebitis	Blood and lymphatic system disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0011 events1 affected74 at risk
Pericardial Effusion	Cardiac disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected74 at risk
Heart Failure	Cardiac disorders	CTCAE 3.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected74 at risk
Myocardial Infarct	Cardiac disorders	CTCAE 3.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0012 events2 affected74 at risk
Colitis	Gastrointestinal disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected74 at risk
Pancreatitis	Gastrointestinal disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected74 at risk
GI perforation	Gastrointestinal disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected74 at risk
GI disorder	Gastrointestinal disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected74 at risk
Arthritis	Musculoskeletal and connective tissue disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected74 at risk
Cerebrovascular Accident	Nervous system disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected74 at risk
Ileus	Gastrointestinal disorders	CTCAE 3.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected74 at risk
Chest pain	Cardiac disorders	CTCAE 3.0	Systematic Assessment	EG0003 events3 affected75 at risk EG0011 events1 affected74 at risk

ID	Term
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D010049	Ovarian Diseases
D000291	Adnexal Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D000091662	Genital Diseases
D004700	Endocrine System Diseases
D006058	Gonadal Disorders

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D056831	Coordination Complexes

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm 1	Docetaxel 30 mg/m2 intravenously (IV) on Days 1 and 8, combined with carboplatin area under the concentration versus time curve (AUC) 6 IV on Day 1, repeated every 21 days for 6 cycles or until disease progression (DP) (whichever occurred first).			16	75	61	75
EG001	Arm2	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.			18	74	61	74

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hematologic toxicity	Blood and lymphatic system disorders	CTCAE 3.0	Systematic Assessment	EG00061 affected75 at risk EG00161 affected74 at risk
Neurotoxicity	Nervous system disorders	CTCAE 3.0	Systematic Assessment	EG00025 affected75 at risk EG00131 affected74 at risk
Hepatic	Hepatobiliary disorders	CTCAE 3.0	Systematic Assessment	EG00011 affected75 at risk EG00113 affected74 at risk